The longterm goals of our work are to understand the basis of immunity to human herpesviruses and to identify mechanisms of latency of these viruses with a view toward controlling the infections they cause. Our emphasis is on studying immunosuppressed patients to define the critical host defenses and sites of latent infection. We plan to prospectively assess the relationship of HSV, VZ and CMV humoral and cellular immune responses (lymphocyte transformation and interferon production) to the clinical infections caused by such agents in heart transplant and lymphoma patients. In regard to the cellular immune responses, an effort will be made to determine the role of various lymphoid cells in the responses seen both in normal as well as immunosuppressed individuals. In order to investigate the process by which VZ virus maintains its latency, an in vitro infection model will be established in cultured neural cells with a view towards creating persistent infection. Various immunological, nucleic acid hybridization and cell culture techniques used to evaluate in vitro persistent infection will also be utilized in studies of neural tissues taken from immunosuppressed individuals in an attempt to establish the site of latency of VZ virus. In addition, we will continue to investigate the actions of interferon, particularly in relationship to the immune system, because of its fundamental role in pathogenesis of infection and its increasing clinical utilization. In particular, we plan to determine the cellular source of Type II mouse interferon and continue its purification and comparison with Type I interferon. We are interested in determining the site and mechanism of their immunomodulating actions. We plan further investigations of the mechanism of their cell membrane modifying effects as well as to assess the role of this effect in the antiviral and non-antiviral actions of interferon.